The purpose of this program project grant is to investigate the immunobiology and improve the therapeutic effects of syngeneic, autologous and allogeneic marrow transplantation in clinical malignancy and in disease of bone marrow failure. The proposal is made up of 7 projects: (1) Therapeutic application of marrow tranplantation and supportive program services; (2) Immunogenetics as applied to clinical bone marrow transplantation; (3) Detection of sensitization prior to marrow transplantation and reconstitution of immune function after marrow transplantation; (4) Graft-versus-host reaction and disease (GVHD); (5) Autologous lympho-hematopoietic transplantation; and (7) Radiotherapy as applied to lympho-hematopoietic transplantation. The objective of the various projects are to: (1) Explore the therapeutic potential of cytoreductive treatment combined with syngeneic, autologous, and allogeneic marrow transplantation in human malignancy and in aplastic anemia; (2) Identify and characterize non-HLA and HLA-linked factors that are pertinent to engraftment and GVHD; (3) Make an indepth evaluation of the acquired immune deficiency following marrow transplantation and develop methods of more rapid repair; (4) Examine in depth the nature, prediction, prevention and treatment of GVHD: (5) Further develop the methodology and study the effects of autologous lympho-hematopoietic transplantation in malignancy; (6) Study mechanisms involved in the etiology of aplastic anemia and hematopoietic reconstitution; and (7) Study the effects of fractionated radiotherapy together with chemotherapy in preclinical models.